The nucleus is known to be compartmentalized into units of function(1), but
the processes leading to the spatial organization of chromosomes and nucle
ar compartments are not yet well defined. Here we report direct quantitativ
e analysis of the global structural perturbations of interphase chromosome
and interchromosome domain distribution caused by infection with herpes sim
plex virus-1 (HSV-1). Our results show that the peripheral displacement of
host chromosomes that correlates with expansion of the viral replication co
mpartment (VRC)(2-5) is coupled to a twofold increase in nuclear volume. Li
ve cell dynamic measurements suggest that viral compartment formation is dr
iven by the functional activity of viral components and underscore the sign
ificance of spatial regulation of nuclear activities.